Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration

Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1...

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Auteurs principaux:	Ruirui Wang, Fujing Huang, Wei Wei, Yu Zhou, Zi Ye, Liya Yu, Junyuan Hu, Cheguo Cai
Format:	article
Langue:	EN
Publié:	Frontiers Media S.A. 2021
Sujets:	PD-L1 mammary stem cell mammary regeneration mammary development cross-talk niche Biology (General) QH301-705.5
Accès en ligne:	https://doaj.org/article/5711ff2a33b74d539d154bba5351f0c2
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spelling	oai:doaj.org-article:5711ff2a33b74d539d154bba5351f0c22021-11-05T09:41:54ZProgrammed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration2296-634X10.3389/fcell.2021.772669https://doaj.org/article/5711ff2a33b74d539d154bba5351f0c22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.772669/fullhttps://doaj.org/toc/2296-634XProgrammed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.Ruirui WangFujing HuangWei WeiYu ZhouZi YeLiya YuJunyuan HuCheguo CaiCheguo CaiFrontiers Media S.A.articlePD-L1mammary stem cellmammary regenerationmammary developmentcross-talknicheBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PD-L1 mammary stem cell mammary regeneration mammary development cross-talk niche Biology (General) QH301-705.5
spellingShingle	PD-L1 mammary stem cell mammary regeneration mammary development cross-talk niche Biology (General) QH301-705.5 Ruirui Wang Fujing Huang Wei Wei Yu Zhou Zi Ye Liya Yu Junyuan Hu Cheguo Cai Cheguo Cai Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
description	Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.
format	article
author	Ruirui Wang Fujing Huang Wei Wei Yu Zhou Zi Ye Liya Yu Junyuan Hu Cheguo Cai Cheguo Cai
author_facet	Ruirui Wang Fujing Huang Wei Wei Yu Zhou Zi Ye Liya Yu Junyuan Hu Cheguo Cai Cheguo Cai
author_sort	Ruirui Wang
title	Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
title_short	Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
title_full	Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
title_fullStr	Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
title_full_unstemmed	Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
title_sort	programmed cell death ligand 1 is enriched in mammary stem cells and promotes mammary development and regeneration
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5711ff2a33b74d539d154bba5351f0c2
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Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration

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